Variant 19-32757038-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366102.1(TDRD12):c.773A>G(p.Asp258Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TDRD12
NM_001366102.1 missense, splice_region

Scores

Splicing: ADA: 0.0002354

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.465

Variant links:

Genes affected

TDRD12 (HGNC:25044): (tudor domain containing 12) Predicted to enable ATP binding activity; RNA helicase activity; and nucleic acid binding activity. Predicted to be involved in several processes, including gamete generation; gene silencing by RNA; and piRNA metabolic process. Predicted to be part of PET complex. [provided by Alliance of Genome Resources, Apr 2022]

TDRD12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06801936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD12	NM_001366102.1 link	c.773A>G	p.Asp258Gly	missense_variant, splice_region_variant	8/33	ENST00000639142.2	NP_001353031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TDRD12	ENST00000639142.2 link	c.773A>G	p.Asp258Gly	missense_variant, splice_region_variant	8/33	5	NM_001366102.1	ENSP00000492643.2	A0A1W2PRK2
TDRD12	ENST00000444215.6 link	c.773A>G	p.Asp258Gly	missense_variant, splice_region_variant	8/28	1		ENSP00000416248.2	Q587J7-1
TDRD12	ENST00000647536.1 link	c.773A>G	p.Asp258Gly	missense_variant, splice_region_variant	8/33			ENSP00000496698.1	A0A2R8Y872
TDRD12	ENST00000421545.2 link	c.773A>G	p.Asp258Gly	missense_variant, splice_region_variant	8/13	5		ENSP00000390621.2	Q587J7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398936

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.773A>G (p.D258G) alteration is located in exon 8 (coding exon 8) of the TDRD12 gene. This alteration results from a A to G substitution at nucleotide position 773, causing the aspartic acid (D) at amino acid position 258 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0032

T;.;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

N;.;N

REVEL

Benign

0.018

Sift

Benign

0.15

T;.;T

Sift4G

Benign

0.23

T;.;T

Polyphen

0.0010

B;.;.

Vest4

0.11

MutPred

0.20

Gain of catalytic residue at S259 (P = 0.0974);Gain of catalytic residue at S259 (P = 0.0974);Gain of catalytic residue at S259 (P = 0.0974);

MVP

0.014

ClinPred

0.11

GERP RS

1.0

Varity_R

0.089

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over